Letter from Michael Heidelberger to Charles D. Hurd, Northwestern University
Heidelberger had helped to synthesize cyclooctatetrene, the next higher analog of benzene (consisting of a ring with eight
carbon atoms and four double bonds) during a year of postdoctoral study (1911-12) in the laboratory of the 1915 Nobel Laureate,
Richard Willstatter, at the Federal Polytechnic Institute in Zurich, Switzerland. His research with Willstatter on cyclooctatetrene
was controversial, and was questioned as late as the 1940s by Hugh S. Taylor and Charles D. Hurd. Heidelberger, however,
strongly defended his results, as documented in this letter, pointing out that while Taylor and Hurd showed that cyclooctatetrene
resinifies and degrades at high temperatures, he had worked in cold temperatures continuously for 24 hours to synthesize a
colorless liquid that was both stable and reactive. Heidelberger and Willstatter's results stood, and as a consequence
of their work cyclooctatetrene became a widely used intermediate in organic chemistry.
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1939-11-08 (November 8, 1939)
Hurd, Charles D.
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Medical Subject Headings (MeSH):
The Making of an Immunologist: Heidelberger's Years at the Rockefeller Institute, 1912-1927
Letter from Michael Heidelberger to Hugh S. Taylor, Princeton University (September 9, 1939)
Letter from Hugh S. Taylor, Princeton University to Michael Heidelberger (November 4, 1939)
Letter from Michael Heidelberger to Hugh S. Taylor, Princeton University (November 7, 1939)
Letter from Charles D. Hurd, Northwestern University to Michael Heidelberger (November 29, 1939)
Letter from Richard Willstatter to Michael Heidelberger (March 27, 1940)
I have just read your very interesting paper in the August J. Am. Chem. Soc. On cyclooctatetrene, and inspired by it and other
recently expressed doubts I have taken out my old reprint and tried to think back to the original work.
Taken in the abstract, I do not see how anyone could disagree with you as to the many possible directions that could be taken
by the reactions used by Willstatter and his coworkers in arriving at cyclooctatetrene. There are, however, certain analogies
and observations, also the experimental condtions used, which limit the possibilities.
First, there is the older work of Willstatter on tropilidene, Ann., 1901, 317, 204, in which the cojugated cycloheptatriene
system seemed to be preferentially formed. Then there is the narrow boiling range, 0.5 degrees, of cyclooctriene dibromide,
indicating the preferentially formation of a single isomer, which would most reasonable be by 1,6 addition. Third, all reactions
were carried out at as low termperatures as possible, and in the final Geryk-vacuum demethylation a more stable product was
obtained than at higher termpeartures.
I think, therefore, that is hardly fair to compare this procedure with the outcome of "pyrolyses" at over 200 degrees,
where rearrangements might easily occur.
Also, I do not see how you can say that "the fact that none of the conjugated hydrocarbon came from IX . . ." casts
doubt on the structure of cyclooctatetrene. I should consider it good negative evidence in favor of Willstatter's formulation
if even drastic pyrolysis failed to produce a conjugated system which would be expected to form directly on structural grounds.
As for the result with X, the diquaternary compound leading to tetraene was not a 1,2 isomer, and this might easily influence
the result. Could it not be repeated with the 1, 4 isomer? And might not the percentage of butadiene even from X have been
much larger if the decomposition had been run more comparably according to our directions for the cycloocta-compound.
I am very glad that these questions are being re-examined, and only interesting results can come to light, whatever the final
result. But I do feel that the original work, too, was carried out on a basis carefully reasoned according to the knowledge
of the time, and that doubt arising from reactions occuring at temperatures 100 degrees higher, or even 300 degrees higher,
as has been done in certain catalysis experiments, should be examined in the same spirit of skepticism.
Looking forward to your comments, and hoping you are planning additional experiments,